I have been given mock results from a PCR test on blood samples taken from kidney recipient patients and their donors. The PCR reaction can detect single copies of viral DNA. I have been asked to determine whether 5 patients have been infected with either human herpesvirus 6 (HHV6) or human cytomegalovirus (HCMV) following kidney transplants. I have results for patients pre-transplantation and 1/3 weeks post-transplantation.

The results are as follows:

Donors:

Donor for patient A = HCMV+

Donor for patient B = HCMV+ & HHV6+

Donor for patient C = Neg for both viruses

Donor for patient D = HHV6+

Donor for patient E = HCMV+ & HHV6+

Recipients:

Patient A = HCMV+ before and 1 & 3 weeks post-transplant

Patient B = Neg for both viruses before, then HHV6+ at week 1 & HCMV+ at week 3 following transplantation but negative for HHV6.

Answers: I am guessing that Patient A was re-infected by donor A. Patient B was neg for both viruses, developed HHV6 week 1 but this test was neg week 3 & instead positive for HCMV – these viruses do not disappear, you either have it or don’t so assuming there is no contamination error then what virus did he develop post-transplant?? Patient C was HHV6+ prior to transplant but donor is neg for both, so what virus did he develop following transplant? I can see that Patient D was infected with HHV6 from donor post-transplant. Patient E was infected with HCMV from donor post-transplant.

I am struggling to determine what virus Patient A, B and C was infected with following transplant. Can anyone help? I know almost 100% of us are infected with both viruses but do not cause disease in healthy people, that both latent and active viruses show positive when in blood and that both viruses can re-activate under certain conditions such as via infected organ transplants and immunosuppression.

1 Answer
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I get the feeling that there's something we should probably know from your textbook or notes that you have not included. As-is, here's my best shot:

It is impossible to determine if Patient A was infected by the transplant since the virus they had before the transplant is the same virus carried by the transplant itself. Without running further tests to separate the two lineages you can't tell. It's likely, though.

While HHV6 has been known to precede HCMV in certain cases the conditions don't seem to apply here. My best guess, which is something I'm pretty loathe to say, is that if you're positive the tests are accurate then it's possible that Patient B's immune system alternately suppressed each virus below detectable levels. Since Patient B is receiving donor tissue with both viruses, and transplant patients are put on immunosuppressants following surgery, it could simply be that at first the immune system was capable of dealing with HCMV for the first week, but not HHV6. Then as it adapted to HHV6, HCMV evolved to evade so it showed up on the assays. That is entirely speculative, though. Another explanation might be that the viral titers of HCMV were too low to detect at Week 1, but it had reproduced enough to show up at Week 3 while the immune system dealt with HHV6. There's a lot of information that's missing on how the virii behave, the characteristics of the immunosuppressants given to the patient, and so on.

Patient C was clearly infected with nothing. They already had HHV6, and that's what showed up post-op.

Patient D was infected with HHV6. They had HCMV before, and both after.

Patient E was infected with HCMV, although like Patient A they could have been infected with a different strain of HHV6 as well, but the tests probably aren't specific enough to determine viral lineages for the before and after strains.